Beneficial bacteria can be used to suppress the growth of pathogenic bacteria. Bacteria and other microorganisms are ubiquitous in the environment. The discovery of pathogenic bacteria and the germ theory of disease have had a tremendous effect on health and disease states. Bacteria are a normal part of the environment of all living things. In the gut, these bacteria are not pathogenic under normal conditions, and in fact improve health by rendering the normal intestinal contents less hospitable for disease causing organisms. Disease prevention is accomplished in a number of ways: nutrients are consumed, leaving less for pathogens; conditions are produced, such as pH and oxygen tension, which are not hospitable for pathogens; compounds are produced that are toxic to pathogens; pathogens are consumed as food by these microorganisms; less physical space remains available for pathogens; and specific binding sites are occupied leaving fewer binding sites available for pathogens. The presence of these desirable bacteria is seen as useful in preventing disease states.
There is a need in the art for improved beneficial bacteria that can suppress the growth of pathogenic bacteria, for example, with regard to the treatment of skin conditions, e.g., acne, e.g., acne vulgaris.
Acne is the most common skin disease and the top reported cause for dermatologist visitations, accounting for about one-fourth of U.S. dermatologists' patient volume. Traditionally thought of as a trivial, “normal” condition, acne has recently been medically redefined to be a chronic disease, one that can significantly impact an individual's quality of life with social, psychological and emotional impairments that are comparable to those reported by patients with epilepsy, asthma, diabetes or arthritis. In the United States alone, acne affects approximately 40 to 50 million people, 20-25% suffer from moderate-to-severe acne. U.S. sales of the Top 10 Branded acne therapeutics have a $3 billion run rate and are comprised of $1.5 billion in systemic retinoids, $700 million in oral antibiotics, $600 million in topic antibiotics and $240 million in topical retinoids. Globally, the prevalence of acne is approximately 80% among adolescents and 50% among young adults. Despite the significant spend on prescription and over the counter remedies, acne remains an area of significant unmet medical need as treatments are either marginally effective (topical antibiotics, topical retinoids, astringents) and/or associated with serious risks (oral retinoids). In addition to the need for a safe and effective product to prevent and treat inflammatory and non-inflammatory acne lesions, there is a substantial unmet need and commercial opportunity for a topical therapy that targets excess sebum production.
TABLE 1Acne SeverityMildModerateComedonalMixed andSevereblackheads/white headspapular/pustularNodularNodular/conglobateFirst-lineTopicalTopical retinoid +Oral antibiotic +Oral antibiotic +Oralretinoidtopical antimicrobialtopical retinoid +/−topical retinoid +/−isotretinoin3benzoyl peroxidebenzoyl peroxideSecond-line/Alternative topicalAlternative topicalAlternative oralOral isotretinoin orHigh dose oralAlternatives1retinoid or azelaicretinoid;antibiotic +alternative oralantibiotic +acid or salicylicantimicrobial agent +alternative topicalantibiotic +topical retinoid +acidalternative topicalretinoid +/−alternative topicalbenzoyl peroxideretinoid or azelaicbenzyoly peroxideretinoid +/−acidbenzoyl peroxideazelaic acidAlternativesSee first-lineSee first-lineOral anti-androgen5 +Oral anti-androgen5 +High dose oralfor females1,4optionsoptionstopical retinoid/topical retinoid/anti-androgen +azelaic acid +/−azelaic acid +/−topical retinoid +/−topical antimicrobialtopical antimicrobialalternative topicalantimicrobialMaintenanceTopical retinoidTopical Retinoid +/− benzoyl peroxidetherapy:Source: Global Data; adapted from AcneAcademy, 2010.1consider physical removal of comedones;2 - with small nodules (<.5 cm);3second course in case of relapse;4for pregnancy; options are limited;5for further information refer to Gollnick et al., 2003.
An ideal target product may have one or more of the following properties: self-administered (e.g., once daily, e.g., twice daily); odorless, colorless and invisible; not associated with increased sensitivity to sunlight; safe, non-toxic if ingested/inhaled and well tolerated on the skin, adjacent mucous membranes and eyes; suitable for both treatment and maintenance therapy without the risk of fostering antibiotic resistance; and acts locally to (in order of priority): reduce the frequency of lesions (antibiotic, anti-inflammatory); reduce the duration of lesions (improved healing); reduce the inflammation of lesions (anti-inflammatory); potentially prevent or reduce aberrant pigmentation and scarring (improved healing); speed the healing of damaged skin (improved healing); reduce the production of excess sebum; and decrease the presence of pathogenic bacteria (antibiotic).